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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >THE ROLE OF CHOROID PLEXUS IN IVIG-INDUCED BETA-AMYLOID CLEARANCE
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THE ROLE OF CHOROID PLEXUS IN IVIG-INDUCED BETA-AMYLOID CLEARANCE

机译：卵泡丛在IVIG诱导的β-淀粉样清除中的作用

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We have shown that intravenous immunogiobulin (IVIG) contains anti-Ap autoantibodies and IVIG could induce beta amyloid (Ap) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Ap efflux remains unclear. In this study, we used amyloid precursor protein (ApPP) transgenic mice to investigate if the IVIG could induce efflux of Ap from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Ap transporter in blood-CSF barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain Ap levels by pulling Ap into the blood system in ApPP transgenic mice. In the mechanistic study, IVIG could induce Ap efflux through the in vitro BCB membrane formed by cultured BCB epithelial cells. Both receptor-associated protein (RAP; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Ap efflux. Should Ap prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for AD by inducing efflux of Ap from the brain through the LRP1 in the BCB.
机译：我们已经显示，静脉内免疫球蛋白（IVIG）包含抗Ap自身抗体，并且IVIG可以在多发性硬化症（MS）和阿尔茨海默氏病（AD）患者中诱导从脑脊液（CSF）到血液的β淀粉样蛋白（Ap）外流。但是，IVIG诱导的Ap外排的分子机制尚不清楚。在这项研究中，我们使用了淀粉样前体蛋白（ApPP）转基因小鼠来研究IVIG是否可以诱导大脑中的Ap流出，以及是否存在低密度脂蛋白受体相关蛋白1（LRP1）（一种假想的Ap转运蛋白在血液中）。脑脊液屏障（BCB）;可以调解此清除程序。我们目前提供有力的证据来证明IVIG可通过将Ap引入ApPP转基因小鼠的血液系统来降低脑Ap水平。在机理研究中，IVIG可通过培养的BCB上皮细胞形成的体外BCB膜诱导Ap流出。受体相关蛋白（RAP; LRP1的功能抑制剂）和LRP1 siRNA均能够显着抑制Ap外排。如果Ap被证明是AD的根本原因，那么我们的结果强烈暗示IVIG通过诱导BC通过LRP1从大脑中引出Ap可能对AD治疗有益。

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